The regulation of bone resorption and formation by systemic hormones and local factors will be studied using animal models and organ and cell cultures. The effects of local factors including prostaglandins, macromolecular stimulators and inhibitors of bone resorption will be examined. The products of arachidonic acid metabolism in bone will be characterized and the effects of eiconsanoids on bone formation analyzed. The relation of local stimulators and inhibitors to osteoclast activating factor and other stimulators of bone resorption will be examined both chemically and biologically. Studies on systemic hormones will include analysis of the anabolic effect of PTH, the paradoxical osteomalacia produced by toxic doses of 1,25-(OH)2D and studies on the mechanism of escape from calcitonin. Glucocorticoids will be analyzed for their dual effects and for their relation to changes in endogenous prostaglandin production. New models will be developed for the study of hormonal regulation of mineralization and for the analysis of the role of sex hormones in bone metabolism. These studies are intended to increase our understanding of physiologic and pathologic regulation of bone metabolism and to provide new insight in the pathogenesis of metabolic bone disease.